Exploring metabolic pathways that contribute to the stem cell phenotype

Background: Stem cells must negotiate their surrounding nutritional and signaling environment and respond accordingly to perform various functions. Metabolic pathways enable these responses, providing energy and biosynthetic precursors for cell proliferation, motility, and other functions. As a result, metabolic enzymes and the molecules which control them are emerging as attractive targets for the manipulation of stem cells. To exploit these targets a detailed characterization of metabolic flux regulation is required. Scope of review: Here we outline recent advances in our understanding of metabolism in pluripotent stem cells and adult progenitors. We describe the regulation of glycolysis, mitochondrial metabolism, and the redox state of stem cells, highlighting key enzymes and transcription factors involved in the control of these pathways. Major conclusions: A general description of stem cell metabolism has emerged, involving increased glycolysis, limited oxidative metabolism, and resistance to oxidative damage. Moving forward, the application of systems-based approaches to stem cells will help shed light on metabolic pathway utilization in proliferating and quiescent stem cells. General significance: Metabolic flux contributes to the unique properties of stem cells and progenitors. This review provides a detailed overview of how stem cells metabolize their surrounding nutrients to proliferate and maintain lineage homeostasis. This article is part of a Special Issue entitled Biochemistry of Stem Cells. (C) 2012 Elsevier B.V. All rights reserved.